1. Field of the Invention
This invention resides in the field of biochemical laboratory equipment, and particularly equipment that is used for analyses of multitudes of small samples of biologically derived materials.
2. Description of the Prior Art
Many biochemical laboratories perform procedures that involve analyses of large numbers of samples, each containing biological species that are very similar in structure and each available only in very small quantities. Analyses of this kind are performed in a sequence of stages, each stage requiring close control of the reaction conditions while maintaining individual handling of each sample. To accomplish this, the samples are often arranged in two-dimensional arrays, and sophisticated instrumentation, frequently involving robotics, is used to remove individual samples from an array and transport the samples to various stations where the different stages of the procedure are performed. Proteomics is an example of such a procedure. The species to be isolated in proteomics typically reside in spots on a two-dimensional gel or on a membrane to which the spots have been transferred from a gel. Polyvinylidene difluoride (PVDF) and nitrocellulose are examples of materials from which such membranes are made. The individual stages in a proteomics procedure include imaging of the array and location of the spots, plus excision of the spots from the array, transfer of the excised spots to various locations, digestion of the substances contained in the spots, and analysis of the digested substances, all performed by the instrument under computer control. The digestion and analysis steps are typically performed in the wells of a multi-well plate such as a 96-well microplate, and excision of the spots from the membrane and transfer to the wells are performed by an automated spot cutter which is controlled by the robotics.
The typical spot cutter includes a cutting tool that terminates in a hollow cylinder that is approximately the size of a hypodermic needle. The tool is movable in the x-y plane for positioning over individual spots, and in the z-direction to be lowered onto the gel or membrane to cut a very small disk containing the spot from the gel or membrane. Disclosures of robotics-containing instrumentation for performing this task are found in International Patent Publication No. WO 99/15875, MacQuarie Research Ltd., applicant, publication date 1 Apr. 1999 (“Apparatus for Removing a Sample From an Array of Samples and a Cutting Tool for Use With That Apparatus”), and in International Patent Publication No. WO 00/57153, Campbell Corporation Pty. Ltd., applicant, publication date 28 Sep. 2000 (“Improvements in Apparatus and Method for Removing Samples”). An example of instrumentation that incorporates disk-excising robotics is the 2DiD integrated system for imaging and spot-picking of LEAP Technologies (Carrboro, N.C., USA). Other examples of spot cutters for use in proteomics are the ProteomeWorks™ Plus Spot Cutter and the EXQuest™ Spot Cutter, both of Bio-Rad Laboratories, Inc., Hercules, Calif., USA.
To facilitate the cutting operation, the gel or membrane is placed on a rigid surface, such as that of a polycarbonate sheet, and the cutting tool is lowered onto and pressed against the surface, causing the cylinder to cut through the gel or membrane to remove a spot in the shape of a disk the size of the cylinder interior. A risk in this operation is that the cutting of the spot may be incomplete, thereby preventing the spot from being fully liberated from the remainder of the gel or membrane. This can occur when the cylinder is not exactly perpendicular to the rigid surface underlying the gel or membrane. A lack of perpendicularity can also cause a partially cut piece to be pulled out of the cylinder tip as the cutting tool is being lifted away. Even if full separation is achieved, an angled cylinder can also cause the cut piece to enter the cylinder at an angle that might interfere with the proper ejection of the piece or that might prevent ejection entirely. Another risk in this procedure is that the cutting edge may scratch the support surface. This can compromise the reliability of the operation for subsequent gels or membranes.